During the progressive stage, the compensatory mechanisms begin failing to meet tissue metabolic needs, and the shock cycle is perpetuated (Concept Map: Shock). As tissue perfusion becomes ineffective, the cells switch from aerobic to anaerobic metabolism to produce energy. Anaerobic metabolism produces small amounts of energy but large amounts of lactic acid, producing lactic acidemia. Increased vascular permeability from endothelial and epithelial hypoxia and inflammatory mediators results in intravascular hypovolemia, tissue edema, and further decline in tissue perfusion.1,2 A systemic release of inflammatory mediators in response to tissue hypoxia, especially in gut tissue, produces microcirculatory impairment and derangement of cellular metabolism, facilitating progression of the shock cycle.^1–3 The patient is experiencing the systemic inflammatory response syndrome (SIRS), and irreversible damage begins to occur. Some cells die as a result of apoptosis, an injury-activated, preprogrammed cellular suicide. Others die as the sodium-potassium pump in the cell membrane fails, causing the cell and its organelles to swell. Cellular energy production comes to a complete halt as the mitochondria swell and rupture. At this point, the problem becomes one of oxygen use instead of oxygen delivery. Even if the cell were to receive more oxygen, it would be unable to use it because of damage to the mitochondria. The cell’s digestive organelles swell and leak destructive enzymes into the cell, accelerating cell death.³

Every system in the body is affected by this process (Box 26-1). Cardiac dysfunction develops as a result of the release of myocardial depressant cytokines.^1,2 Ventricular failure eventually occurs, further perpetuating the entire process. Central nervous system (CNS) dysfunction develops as a result of cerebral hypoperfusion, leading to failure of the SNS, cardiac and respiratory depression, and thermoregulatory failure. Endothelial injury from hypoxia and inflammatory cytokines and impaired blood flow result in microvascular thrombosis. Hematological dysfunction occurs as a result of consumption of clotting factors, release of inflammatory cytokines, and dilutional thrombocytopenia. Disseminated intravascular coagulation (DIC) eventually may develop. Pulmonary dysfunction occurs as a result of increased pulmonary capillary membrane permeability, pulmonary microemboli, and pulmonary vasoconstriction. Ventilatory failure and acute lung injury (ALI) develop. Renal dysfunction develops as a result of renal vasoconstriction and renal hypoperfusion, leading to acute tubular necrosis (ATN). Gastrointestinal dysfunction occurs as a result of splanchnic vasoconstriction and hypoperfusion and leads to failure of the gut organs. Disruption of the intestinal epithelium releases gram-negative bacteria into the system, which further perpetuates the entire shock syndrome.⁴

During the refractory stage, shock becomes unresponsive to therapy and is considered irreversible. As the individual organ systems die, MODS—defined as failure of two or more body systems—occurs. Death is the final outcome. Regardless of the etiological factors, death occurs from ineffective tissue perfusion because of the failure of the circulation to meet the oxygen needs of the cell.³

The patient with a mean arterial blood pressure (MAP) less than 60 mm Hg or with evidence of multisystem organ hypoperfusion is considered to be in a shock state.1,5 Because shock is a dynamic physiological phenomenon, hypotension may occur late in the process.⁶ Clinical manifestations vary according to the underlying cause of shock, the stage of the shock, and the patient’s response to shock.

Compensatory mechanisms may produce normal hemodynamic values even when tissue perfusion is compromised.^4–7 Global indicators of systemic perfusion and oxygenation include serum lactate, arterial base deficit, serum bicarbonate, and central or mixed venous oxygen saturation levels. Inadequate cellular oxygenation with anaerobic metabolism and increased metabolic lactate production increase the serum lactate level.⁸ The level and duration of this hyperlactatemia are predictive of morbidity and mortality.^7–11 The base deficit derived from arterial blood gas (ABG) values also reflects global tissue acidosis and is frequently used to assess the severity of shock.^6,7,9 Studies have demonstrated serum bicarbonate to be an equivalent alternative to arterial base deficit in predicting mortality in surgical and trauma patients.^12,13 The use of mixed venous oxygen saturation (SvO₂) measured by means of a pulmonary artery catheter or central venous oxygen saturation (SCvO₂) measured with a central venous catheter allows assessment of the balance of oxygen delivery and oxygen consumption and the ratio of oxygen extraction.^14–16 After years of recommended use to guide the care of patients with severe sepsis, this measure of global oxygen balance is being evaluated for use in other critically ill populations.^15–21 The sections on different types of shock discuss clinical assessment and diagnosis of the patient in shock.

The major focus of the treatment of shock is the improvement and preservation of tissue perfusion. Adequate tissue perfusion depends on an adequate supply of oxygen being transported to the tissues and the cell’s ability to use it. Oxygen transport is influenced by pulmonary gas exchange, CO, and hemoglobin level. Oxygen use is influenced by the internal metabolic environment. Management of the patient in shock focuses on supporting oxygen delivery.1,22

Adequate pulmonary gas exchange is critical to oxygen transport. Establishing and maintaining an adequate airway are the first steps in ensuring adequate oxygenation. After the airway is patent, emphasis is placed on improving ventilation and oxygenation. Therapies include administration of supplemental oxygen and mechanical ventilatory support.

An adequate CO and hemoglobin level are crucial to oxygen transport. CO depends on heart rate, preload, afterload, and contractility. A variety of fluids and drugs are used to manipulate these parameters. The types of fluids used include crystalloids and colloids. The categories of drugs used include vasoconstrictors, vasodilators, positive inotropes, and antidysrhythmics.

Fluid administration is indicated for decreased preload related to intravascular volume depletion, and it can be accomplished by use of a crystalloid or colloid solution, or both. Crystalloids are balanced electrolyte solutions that may be hypotonic, isotonic, or hypertonic. Examples of crystalloid solutions used in shock situations are normal saline and lactated Ringer’s solution. Colloids are protein- or starch-containing solutions. Examples of colloid solutions are blood and blood components, such as albumin, and pharmaceutical plasma expanders, such as hetastarch, dextran, and mannitol.

The choice of fluid is a subject of debate and depends on the situation.^15,23–25 Fluid resuscitation with normal saline or with albumin produces similar outcomes regardless of baseline serum albumin level, and both are considered safe.^26,27 Crystalloid solutions are inexpensive and effective. Advantages of colloids include faster restoration of intravascular volume and use of smaller amounts. Colloids are believed to stay in the intravascular space, unlike crystalloids, which readily leak into the extravascular space. Disadvantages include expense, allergic reactions, and difficulties in typing and cross-matching blood. Colloids also can leak out of damaged capillaries and cause a variety of additional problems, particularly in the lungs.

Blood should be considered to augment oxygen transport if the patient’s hemoglobin level is critically low, although controversy exists about what threshold value should be used.^4,15 Transfusion of stored red blood cells does not substantially increase oxygen consumption and has been associated with immunosuppression, infection, impairment of microcirculatory flow, coagulopathy, and increased mortality. Restrictive transfusion practice has demonstrated lower mortality.^4,16,28 Transfusion-related acute lung injury (TRALI) resulting from immune and nonimmune neutrophil activation has become the leading cause of transfusion-related death and may occur with transfusion of any plasma-containing blood or blood product.^28–30

Vasoconstrictor agents are used to increase afterload by increasing the systemic vascular resistance (SVR) and improving the patient’s blood pressure level. Vasodilator agents are used to decrease preload or afterload, or both, by decreasing venous return and SVR. Positive inotropic agents are used to increase contractility. Antidysrhythmic agents are used to influence heart rate.³¹ Box 26-2 provides examples of each of these agents.

Sodium bicarbonate is not recommended in the treatment of shock-related lactic acidosis.^16,32,33 No overall benefit has been found, and the risks associated with its use are significant. They include shifting of the oxyhemoglobin dissociation curve to the left, rebound increase in lactic acid production, development of hyperosmolar state, fluid overload resulting from excessive sodium, and rapid cellular electrolyte shifts.^11,32,33

The patient should be started on nutritional support therapy as early as possible. The type of nutritional supplementation initiated varies according to the cause of shock, and it should be tailored to the individual patient’s needs, as indicated by the underlying condition and laboratory data. The enteral route is preferred over the parenteral, although parental nutrition should be considered when enteral feeding is contraindicated.^25,34–37 Supplementation of enteral feeding with parenteral nutrition to increase caloric intake should be considered but has not been shown to improve patient outcomes.^35–37

Glucose control is recommended for all critically ill patients.^38,39 Benefits of glucose control in the critically ill include lower incidences of infection, renal failure, sepsis, polyneuropathy, need for blood transfusion, prolonged mechanical ventilation, and death.^38–42

The psychosocial needs of the patient and family dealing with shock are extremely important. These needs are based on situational, familial, and patient-centered variables. Nursing priorities in managing the patient in shock are directed toward (1) providing information on patient status, (2) explaining procedures and routines, (3) supporting the family, (4) encouraging the expression of feelings, (5) facilitating problem solving and shared decision making, (6) individualizing visitation schedules, (7) involving the family in the patient’s care, and (8) establishing contacts with necessary resources.43 Patients and families should be given the option of family presence during invasive procedures and resuscitation.^43–45 Collaborative management of the patient with shock is outlined in the Collaborative Management Box on Shock.

Hypovolemic shock can result from absolute or relative hypovolemia. Absolute hypovolemia occurs when there is a loss of fluid from the intravascular space. This can result from an external loss of fluid from the body or from internal shifting of fluid from the intravascular space to the extravascular space. Fluid shifts can result from a loss of intravascular integrity, increased capillary membrane permeability, or decreased colloidal osmotic pressure. Relative hypovolemia occurs when vasodilation produces an increase in vascular capacitance relative to circulating volume (Box 26-3).

Hypovolemia results in a loss of circulating fluid volume. A decrease in circulating volume leads to a decrease in venous return, which results in a decrease in end-diastolic volume or preload. Preload is a major determinant of stroke volume (SV) and CO. A decrease in preload results in a decrease in SV and CO. The decrease in CO leads to inadequate cellular oxygen supply and ineffective tissue perfusion (Figure 26-1).

The clinical manifestations of hypovolemic shock depend on the severity of fluid loss and the patient’s ability to compensate for it. Clinical classes have been developed by the American College of Surgeons to describe the levels of severity of hypovolemic shock. Class I indicates a fluid volume loss up to 15% or an actual volume loss up to 750 mL. Compensatory mechanisms maintain CO, and the patient appears free of symptoms other than slight anxiety.4,46

Class II hypovolemia occurs with a fluid volume loss of 15% to 30% or an actual volume loss of 750 to 1500 mL. Falling CO activates more intense compensatory responses. The heart rate increases to more than 100 beats/minute in response to increased SNS stimulation unless blocked by preexisting beta-blocker therapy. The pulse pressure narrows as the diastolic blood pressure increases because of vasoconstriction. The respiratory rate increases to 20 to 30 breaths/minute, and respiratory depth increases in an attempt to improve oxygenation. ABG specimens drawn during this phase reveal respiratory alkalosis and hypoxemia, as evidenced by a low partial pressure of carbon dioxide (PaCO₂) and a low partial pressure of oxygen (PaO₂), respectively. Urine output starts to decline to 20 to 30 mL/hour as renal perfusion decreases. The urine sodium level decreases, whereas urinary osmolality and specific gravity increase as the kidneys start to conserve sodium and water. The patient’s skin becomes pale and cool with delayed capillary refill because of peripheral vasoconstriction. Jugular veins appear flat as a result of decreased venous return.^4,46

Hypovolemic shock that is class III occurs with a fluid volume loss of 30% to 40% or an actual volume loss of 1500 to 2000 mL. This level of severity produces the progressive stage of shock as compensatory mechanisms become overwhelmed and ineffective tissue perfusion develops. Blood pressure decreases. The heart rate increases to more than 120 beats/minute, and dysrhythmias develop as myocardial ischemia ensues. Respiratory distress occurs as the pulmonary system deteriorates. ABG values during this phase reveal respiratory and metabolic acidosis and hypoxemia, as evidenced by a high PaCO₂, low bicarbonate (HCO₃^–), and low PaO₂, respectively. Decreased renal perfusion results in the development of oliguria. Blood urea nitrogen (BUN) and serum creatinine levels start to rise as the kidneys begin to fail. The patient’s skin becomes ashen, cold, and clammy, with marked delayed capillary refill. The patient appears confused as cerebral perfusion decreases and the level of consciousness deteriorates.^4,46

Class IV hypovolemic shock is usually refractory in nature. It occurs with a fluid volume loss of greater than 40% or an actual volume loss of more than 2000 mL. The compensatory mechanisms of the body completely deteriorate, and organ failure occurs.⁵ Severe tachycardia and hypotension ensue. Peripheral pulses are absent, and because of marked peripheral vasoconstriction, capillary refill does not occur. The skin appears cyanotic, mottled, and extremely diaphoretic. Urine output ceases. The patient becomes lethargic and unresponsive, and various clinical manifestations associated with failure of the different body systems develop.^4,46

Assessment of the hemodynamic parameters of a patient in hypovolemic shock varies by stage but commonly reveals a decreased CO and cardiac index (CI). Loss of circulating volume leads to a decrease in venous return to the heart, which results in a decrease in the preload of the right and left ventricles. This is evidenced by a decline in the central venous pressure (CVP) or right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP). Vasoconstriction of the arterial system results in an increase in the afterload of the heart, as evidenced by an increase in the SVR. This vasoconstriction may produce a falsely elevated systolic blood pressure when measured by arterial catheter. MAP is more accurate in this low-flow state.⁵

Aggressive fluid resuscitation in trauma and surgical patients is the subject of great debate. The benefit of limited or hypotensive (systolic blood pressure >80 mm Hg) volume resuscitation in patients with uncontrolled hemorrhage is postulated to lessen bleeding and improve survival.22,47–49 The type and amount of solutions used for fluid resuscitation and the rate of administration influence immune function, inflammatory mediator release, coagulation, and the incidence of cardiac, pulmonary, and gastrointestinal complications.^{23,24,50–52} Consensus on the optimal resuscitative strategy for hypovolemic shock is lacking.^23,24,48

Measures to minimize fluid loss include limiting blood sampling, observing lines for accidental disconnection, and applying direct pressure to bleeding sites. Measures to facilitate the administration of volume replacement include insertion of large-bore peripheral intravenous catheters, rapid administration of prescribed fluids, and positioning the patient with the legs elevated, trunk flat, and head and shoulders above the chest. Monitoring the patient for clinical manifestations of fluid overload or complications related to fluid and blood product administration is essential for preventing further problems.

Cardiogenic shock can result from primary ventricular ischemia, structural problems, and dysrhythmias.53,54 The most common cause is acute MI resulting in the loss of 40% or more of the functional myocardium. It can occur with ST-elevation or non-ST-elevation MI.^54,57 The damage to the myocardium may occur after one massive MI (usually of the anterior wall), or it may be cumulative as a result of several smaller MIs or a small MI in a patient with preexisting ventricular dysfunction.^53,57 End-stage cardiomyopathy may also cause cardiogenic shock as may structural problems of the cardiopulmonary system and dysrhythmias if they disrupt the forward motion of the blood through the heart (Box 26-4).^53,54,57

Cardiogenic shock results from the impaired ability of the ventricle to pump blood forward, which leads to a decrease in SV and an increase in the blood left in the ventricle at the end of systole. The decrease in SV results in a decrease in CO, which leads to decreased cellular oxygen supply and ineffective tissue perfusion. Typically, myocardial performance spirals downward as compensatory vasoconstriction increases myocardial afterload and low blood pressure worsens myocardial ischemia. Evidence of SIRS has been observed in a substantial number of patients with cardiogenic shock.55,57–59 Activation of inflammatory cytokines induce systemic vasodilation, defective cellular oxygen use, and occasionally, normalization of the CO. Whether this process contributes to the genesis or the outcome of cardiogenic shock is uncertain, but it is thought to be activated by acute MI and to facilitate development of sepsis.^55,57,58 As left ventricular contractility declines and ventricular compliance decreases, an increase in end-systolic volume results in blood backing up into the pulmonary system and the subsequent development of pulmonary edema. Pulmonary edema causes impaired gas exchange and decreased oxygenation of the arterial blood, which further impair tissue perfusion (Figure 26-2). Death due to cardiogenic shock may result from multiple organ failure or cardiopulmonary collapse.^55,58

A variety of clinical manifestations occur in the patient in cardiogenic shock, depending on etiological factors in pump failure, the patient’s underlying medical status, and the severity of the shock state. Some clinical manifestations are caused by failure of the heart as a pump, whereas many are related to the overall shock response (Box 26-5).

Initially, clinical manifestations reflect the decline in CO. These signs and symptoms include systolic blood pressure less than 90 mm Hg or an acute drop in systolic or mean blood pressure of 30 mm Hg or more; decreased sensorium; cool, pale, moist skin; and urine output of less than 30 mL/hour.^57,60 The patient also may complain of chest pain. Tachycardia develops to compensate for the decrease in CO. A weak, thready pulse develops, and diminished S₁ and S₂ heart sounds may occur as a result of the decreased contractility. The respiratory rate increases to improve oxygenation. ABG values at this point indicate respiratory alkalosis, as evidenced by a decrease in PaCO₂. Urinalysis findings demonstrate a decrease in urine sodium level and an increase in urine osmolality and specific gravity as the kidneys start to conserve sodium and water. The patient also may experience a variety of dysrhythmias, depending on the underlying problem.⁵⁴

As the left ventricle fails, auscultation of the lungs may disclose crackles and rhonchi, indicating the development of pulmonary edema. Hypoxemia occurs, as evidenced by a fall in PaO₂ and SaO₂ as measured by ABG values. Heart sounds may reveal an S₃ and S₄. Jugular venous distention is evident with right-sided failure.

Assessment of the hemodynamic parameters of a patient in cardiogenic shock reveals a decreased CO with a CI less than 2.2 L/minute/m² in the presence of an elevated PAOP of more than 15 to 18 mm Hg.^53,54,57,59 A proportional pulse pressure (systolic BP/pulse pressure) less than 25% is indicative of left ventricular failure and a CI less than 2.2 and may be useful when direct measurement of CI is unavailable.⁶¹ Increased filling pressures are necessary to rule out hypovolemia as the cause of circulatory failure. The increase in PAOP reflects an increase in the left ventricular end-diastolic pressure (LVEDP) and left ventricular end-diastolic volume (LVEDV) resulting from decreased SV. With right ventricular failure, the RAP also increases. Compensatory vasoconstriction results in an increase in the afterload of the heart, as evidenced by an increase in the SVR. Echocardiography confirms the diagnosis of cardiogenic shock and rules out other causes of circulatory failure.^53,54,57

As compensatory mechanisms fail and ineffective tissue perfusion develops, other clinical manifestations appear. Myocardial ischemia progresses, as evidenced by continued increases in heart rate, dysrhythmias, and chest pain. Pulmonary function deteriorates, which leads to respiratory distress. ABG values during this phase reveal respiratory and metabolic acidosis and hypoxemia, as indicated by a high PaCO₂, low HCO₃^–, and low PaO₂, respectively. Renal failure occurs, as exhibited by the development of anuria and increases in BUN and serum creatinine levels. Cerebral hypoperfusion manifests as a decreasing level of consciousness.

Treatment of the patient in cardiogenic shock requires an aggressive approach. The major goals of therapy are to treat the underlying cause, enhance the effectiveness of the pump, and improve tissue perfusion. This approach includes identifying the etiological factors of pump failure and administering pharmacological agents to enhance CO. Inotropic agents are used to increase contractility and maintain adequate blood pressure and tissue perfusion. A vasopressor may be necessary to maintain blood pressure when hypotension is severe.57,60 Diuretics are used for preload reduction. After blood pressure has been stabilized, vasodilating agents are used for preload and afterload reduction. Antidysrhythmic agents should be used to suppress or control dysrhythmias that can affect CO.⁵³ Intubation and mechanical ventilation may be necessary to support oxygenation.

Intraaortic balloon pump (IABP) support should be instituted if drug therapy does not quickly reverse the shock state.^54–57 The IABP is a temporary measure to decrease myocardial workload by improving myocardial supply and decreasing myocardial demand. It achieves this goal by improving coronary artery perfusion and reducing left ventricular afterload. Chapter 13 provides more information about IAPB therapy.

After the cause of pump failure has been identified, measures should be taken to correct the problem if possible. If the problem is related to an acute MI, early revascularization by coronary angioplasty or coronary artery bypass surgery provides significant survival benefit.^53–57,62 Thrombolytic agents may be used in select patients. When conventional therapies fail, a ventricular assist device (VAD) or extracorporeal life support with a membrane oxygenator may be used to support the patient in acute cardiogenic shock.^54,57,63,64 These mechanical circulatory assist devices provide an external means to sustain effective organ perfusion, allowing time for the patient’s ventricle to heal or for cardiac transplantation to take place.

Anaphylactic shock is caused by an antibody-antigen response. Almost any substance can cause a hypersensitivity reaction. These substances, known as antigens, can be introduced by injection or ingestion or through the skin or respiratory tract. A number of antigens have been identified that can cause a reaction in a hypersensitive person. This list includes foods, food additives, diagnostic agents, biological agents, environmental agents, drugs, and venoms (Box 26-6).^66–68 In the hospital environment, latex is an extremely problematic antigen for patients and health care providers (Patient Safety Priorities Box on Latex Allergy).

Anaphylactic reactions can be IgE-mediated or non-IgE-mediated responses. IgE is an antibody that is formed as part of the immune response. The first time an antigen enters the body, an antibody IgE, specific for the antigen, is formed. The antigen-specific IgE antibody is then stored by attachment to mast cells and basophils. This initial contact with the antigen is known as a primary immune response. The next time the antigen enters the body, the preformed IgE antibody reacts with it, and a secondary immune response occurs. This reaction triggers the release of biochemical mediators from the mast cells and basophils and initiates the cascade of events that precipitates anaphylactic shock.^66,69,70

Some anaphylactic reactions are non-IgE-mediated responses in that they occur in the absence of activation of IgE antibodies. These responses occur as a result of direct activation of the mast cells to release biochemical mediators. Direct activation of mast cells can be triggered by humoral mediators, such as the complement system and the coagulation-fibrinolytic system. Biochemical mediators can be released as a direct or indirect response to many drugs. This type of reaction, formerly known as anaphylactoid reaction, is produced in persons not previously sensitized, and it can occur with the first exposure to an antigen.^66,68,70

The antibody-antigen response (immunological stimulation) or the direct triggering (nonimmunological activation) of the mast cells results in the release of biochemical mediators. These mediators include histamine, eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor of anaphylaxis (NCF), platelet-activating factor (PAF), proteinases, heparin, serotonin, leukotrienes (also known as slow-reacting substance of anaphylaxis), and prostaglandins. The activation of the biochemical mediators causes vasodilation; increased capillary permeability; laryngeal edema; bronchoconstriction; excessive mucus secretion; coronary vasoconstriction; inflammation; cutaneous reactions; and constriction of the smooth muscle in the intestinal wall, bladder, and uterus. Coronary vasoconstriction causes severe myocardial depression. Cutaneous reactions cause stimulation of nerve endings, followed by itching and pain.65,66,69

ECF-A promotes chemotaxis of eosinophils, facilitating the movement of eosinophils into the area. During allergic reactions, eosinophils phagocytose the antibody-antigen complex and other inflammatory debris and release enzymes that inhibit vasoactive mediators, such as histamine and leukotrienes. Secondary mediators such as bradykinin and plasmin are produced that enhance or inhibit the already released biochemical mediators. Peripheral vasodilation results in relative hypovolemia and decreased venous return. Increased capillary membrane permeability results in the loss of intravascular volume, worsening the hypovolemic state. Decreased venous return results in decreased end-diastolic volume and SV. The decline in SV leads to decreased CO and ineffective tissue perfusion. Death may result from airway obstruction or cardiovascular collapse, or both (Figure 26-3).^65,66,69,70

Anaphylactic shock is a severe systemic reaction that can affect multiple organ systems. A variety of clinical manifestations occur in the patient in anaphylactic shock, depending on the extent of multisystem involvement. The symptoms usually start to appear within minutes of exposure to the antigen, but they may not occur for up to 1 hour (Box 26-7).⁶⁵ Symptoms may also reappear after a 1- to 72-hour window of resolution. These late-phase reactions may be similar to the initial anaphylactic response, milder, or more severe.^65,71

The cutaneous effects may appear first and include pruritus, generalized erythema, urticaria, and angioedema. Commonly seen on the face and in the oral cavity and lower pharynx, angioedema develops as a result of fluid leaking into the interstitial space. The patient may appear restless, uneasy, apprehensive, and anxious and may complain of being warm. Respiratory effects include the development of laryngeal edema, bronchoconstriction, and mucous plugs. Clinical manifestations of laryngeal edema include inspiratory stridor, hoarseness, a sensation of fullness or a lump in the throat, and dysphagia. Bronchoconstriction causes dyspnea, wheezing, and chest tightness.^65,66,69 Gastrointestinal and genitourinary manifestations, which may develop as a result of smooth muscle contraction, include vomiting, diarrhea, cramping, and abdominal pain.

As the anaphylactic reaction progresses, hypotension and reflex tachycardia develop. This occurs in response to massive vasodilation and loss of circulating volume. Jugular veins appear flat as right ventricular end-diastolic volume is decreased. The eventual outcome is circulatory failure and ineffective tissue perfusion.^65,66,69 The patient’s level of consciousness may deteriorate to unresponsiveness.

Assessment of the hemodynamic parameters of a patient in anaphylactic shock reveals a decreased CO and CI. Venous vasodilation and massive volume loss lead to a decrease in preload, which results in a decline in the RAP and PAOP. Vasodilation of the arterial system results in a decrease in the afterload of the heart, as evidenced by a decrease in the SVR. Box 26-8 outlines the clinical criteria for diagnosing anaphylaxis.

Epinephrine is the first-line treatment of choice for anaphylaxis. It promotes bronchodilation and vasoconstriction and inhibits further release of biochemical mediators. In mild cases of anaphylaxis, 0.3 to 0.5 mg (0.3 to 0.5 mL) of a 1 : 1000 dilution of epinephrine is administered by intramuscular injection into the anterolateral thigh and repeated every 5 to 15 minutes until anaphylaxis is resolved.65,66,70–72 Subcutaneous injection is no longer recommended.⁷¹ For anaphylactic shock with hypotension, epinephrine is administered intravenously. The intravenous dose is 0.1 (1 mL) of a 1 : 10,000 dilution administered over 5 minutes. If hypotension persists, a continuous infusion of epinephrine is recommended, administered at 1 to 4 mcg/min with titration up to 10 mcg/min as needed.^66,67,69,73 Patients receiving beta-blockers may have a limited response to epinephrine. Intravenous glucagon administered as a 20 to 30 mcg/kg bolus over 5 minutes followed by continuous infusion at 5 to 15 mcg/minute is recommended for inotropic and vasoactive support for these patients.^65,66,71,73

Diphenhydramine (Benadryl), given 1 to 2 mg/kg (25 to 50 mg) by a slow intravenous route every 4 to 8 hours, is a second-line agent used to block the histamine response.^{65,66,69,71,73} Corticosteroids also may be given with the goal of preventing a delayed reaction and stabilizing capillary membranes.^65,66,71 Fluid replacement is accomplished by use of a crystalloid or colloid solution. Positive inotropic agents and vasoconstrictor agents may be necessary to reverse the effects of myocardial depression and vasodilation.^65,66,69,71

Measures to facilitate ventilation include positioning the patient to assist with breathing and instructing the patient to breathe slowly and deeply. Airway protection through prompt administration of prescribed medications is essential. Measures to facilitate the administration of volume replacement include inserting large-bore peripheral intravenous catheters; rapidly administering prescribed fluids; and positioning the patient with the legs elevated, trunk flat, and head and shoulders above the chest. Measures to promote comfort include administering medications to relieve itching, applying warm soaks to skin, and if necessary, covering the patient’s hands to discourage scratching. Observing the patient for clinical manifestations of a delayed reaction is critical. Patient education about how to avoid the precipitating allergen is essential for preventing future episodes of anaphylaxis.

Neurogenic shock can be caused by anything that disrupts the SNS. The problem can occur as the result of interrupted impulse transmission or blockage of sympathetic outflow from the vasomotor center in the brain.74–76 The most common cause is spinal cord injury. Neurogenic shock may mistakenly be referred to as spinal shock. The latter condition refers to loss of neurological activity below the level of spinal cord injury, but it does not necessarily involve ineffective tissue perfusion.^77–79

Loss of sympathetic tone results in massive peripheral vasodilation, inhibition of the baroreceptor response, and impaired thermoregulation. Arterial vasodilation leads to a decrease in SVR and a fall in blood pressure. Venous vasodilation leads to relative hypovolemia and pooling of blood in the venous circuit. The decreased venous return results in a decrease in end-diastolic volume or preload, causing a decrease in SV and CO. The fall in blood pressure and CO leads to inadequate or ineffective tissue perfusion. Loss of sympathetic tone and inhibition of the baroreceptor response result in bradycardia.74–76,78 The slow heart rate worsens CO, which further compromises tissue perfusion. Impaired thermoregulation occurs because of loss of vasomotor tone in the cutaneous blood vessels that dilate and constrict to maintain body temperature. The patient becomes poikilothermic, or dependent on the environment for temperature regulation (Figure 26-4).

The patient in neurogenic shock characteristically presents with hypotension, bradycardia, and warm, dry skin.74–76 The decreased blood pressure results from massive peripheral vasodilation. The decreased heart rate is caused by inhibition of the baroreceptor response and unopposed parasympathetic control of the heart.⁷⁹ Hypothermia develops from uncontrolled peripheral heat loss. The warm, dry skin occurs as a consequence of pooling of blood in the extremities and loss of vasomotor control in surface vessels of the skin that control heat loss.

Assessment of the hemodynamic parameters of a patient in neurogenic shock reveals a decreased CO and CI. Venous vasodilation leads to a decrease in preload, which results in a decline in the RAP and PAOP. Vasodilation of the arterial system causes a decrease in the afterload of the heart, as evidenced by a decrease in the SVR.⁷⁶

Hypovolemia is treated with careful fluid resuscitation. The minimal amount of fluid is administered to ensure adequate tissue perfusion. Volume replacement is initiated for systolic blood pressure lower than 90 mm Hg, urine output of less than 30 mL/hour, or changes in mental status that indicate decreased cerebral tissue perfusion. The patient is carefully observed for evidence of fluid overload. Vasopressors are used as necessary to maintain blood pressure and organ perfusion.74,76,78 The bradycardia associated with neurogenic shock rarely requires specific treatment, but atropine or electrical pacing can be used when necessary.^69,74 Hypothermia is treated with warming measures and environmental temperature regulation.

Venous pooling in the lower extremities promotes the formation of deep vein thrombosis (DVT), which can result in a pulmonary embolism. All patients at risk for DVT should be started on prophylaxis therapy. DVT-prophylactic measures include monitoring of calf and thigh measurements, passive range-of-motion exercises, application of sequential pneumatic stockings, and administration of prescribed anticoagulation therapy.

Sepsis is caused by a wide variety of microorganisms, including gram-negative and gram-positive aerobes, anaerobes, fungi, and viruses. The source of these microorganisms varies. Exogenous sources include the hospital environment and members of the health care team. Endogenous sources include the patient’s skin, gastrointestinal tract, respiratory tract, and genitourinary tract. In recent years, the incidence of chest-related infections has risen dramatically, and the lungs have replaced the intraabdominal organs as the most common site of infection producing severe sepsis and septic shock.83,84 Gram-positive bacteria are responsible for more than one half of the cases of sepsis.⁸⁵ Sepsis and septic shock are associated with a wide variety of intrinsic and extrinsic precipitating factors (Box 26-10). All of these factors interfere directly or indirectly with the body’s anatomic and physiological defense mechanisms. Several of the intrinsic factors are not modifiable or are very difficult to control. Several of the extrinsic factors may be required for diagnosis and management. All critically ill patients are therefore at risk for septic shock.⁸⁰

The syndrome encompassing severe sepsis and septic shock is a complex systemic response that is initiated when a microorganism enters the body and stimulates the inflammatory/immune system. Shed protein fragments and the release of toxins and other substances from the microorganism activate the plasma enzyme cascades (complement, kinin/kallikrein, coagulation, and fibrinolytic factors), as well as platelets, neutrophils, monocytes, and macrophages. On activation, these systems and cells release a variety of mediators, or cytokines, that initiate a chain of complex interactions leading to a maladaptive SIRS.86–91

After the mediators are activated, a variety of physiological and pathophysiological events occur that affect clotting, the distribution of blood flow to the tissues and organs, capillary membrane permeability, and the metabolic state of the body. Subsequently, a systemic imbalance between cellular oxygen supply and demand develops that results in cellular hypoxia, damage, hibernation, and death (Figure 26-5).^4,88,90,91

Hallmarks of severe sepsis are endothelial damage and coagulation dysfunction.^87,88,92,93 Tissue factor is released from endothelial cells and monocytes in response to stimulation by the inflammatory cytokines.^87,88 Release of tissue factor initiates the coagulation cascade, producing widespread microvascular thrombosis and further stimulation of the systemic inflammatory pathways.⁸⁸ Diffuse endothelial damage impairs endogenous anticlotting mechanisms.⁸⁸ Mediator-induced suppression of fibrinolysis slows clot breakdown. The result is DIC with eventual consumption of coagulation factors, bleeding, and hemorrhage.^92,94

Significant alterations in cardiovascular hemodynamics are caused by the activation of inflammatory cytokines and endothelial damage.^32,88,93 Massive peripheral vasodilation results in the development of relative hypovolemia. Increased capillary permeability produces a loss of intravascular volume to the interstitium, which accentuates the reduction in preload and CO. These changes, coupled with the microvascular thrombosis, produce maldistribution of circulating blood volume, decreased tissue perfusion, and inadequate oxygen delivery to the cells. Microcirculatory shunting is a key feature of this distributive shock.^88,95,96 Impaired ventricular contractility results from cytokine activity.^4,88

Activation of the central nervous and endocrine systems also occurs as part of the response to invading microorganisms. This activation leads to stimulation of the SNS and the release of ACTH. These events trigger the release of epinephrine, norepinephrine, glucocorticoids, aldosterone, glucagon, renin, and growth hormone resulting in the development of a hypermetabolic state and contributing to vasoconstriction of the renal, pulmonary, and splanchnic beds. Selective vasoconstriction in the splanchnic bed may contribute to hypoperfusion of the gastric mucosa. The resulting gut injury propagates the inflammatory response.^2,97

Several metabolic alterations occur as a result of CNS, endocrine system, and cytokine activation. The hypermetabolic state increases energy expenditure and oxygen demand, and it contributes to cellular hypoxia. Lactic acid is produced as a result of increased metabolic lactate production and hypoxic anaerobic metabolism. Glucocorticoids, ACTH, epinephrine, glucagon, and growth hormone are all catabolic hormones that are released as part of this response. In conjunction with the inflammatory cytokines, these hormones stimulate catabolism of protein stores in the visceral organs and skeletal muscles to fuel glucose production in the liver, hyperglycemia, and insulin resistance.⁸ The cytokines also stimulate the use of fats for energy production (lipolysis).^8,91,98

Metabolic derangements in severe sepsis and septic shock include an inability of the cells to use oxygen even if blood flow is adequate. Mitochondrial dysfunction is thought to be the underlying mechanism.^88,91,98 This bioenergetic failure plays an important role in the development of multiple organ dysfunction.^88,91,98 The exaggerated inflammatory response in severe sepsis results in apoptosis, a programmed cell death or cellular suicide affecting endothelial and immune cells in particular.^88,91,93

These complex and interrelated pathophysiological changes associated with severe sepsis and septic shock produce a pathological imbalance between cellular oxygen demand and cellular oxygen supply and consumption. If unabated, this situation ultimately results in tissue ischemia, MODS, and death.

Effective treatment of severe sepsis and septic shock depends on timely recognition. The diagnosis of severe sepsis is based on the identification of three conditions: known or suspected infection, two or more of the clinical indications of the systemic inflammatory response, and evidence of at least one organ dysfunction. Clinical indications of systemic inflammatory response and sepsis were included in the original ACCP/SCCM consensus definitions and are listed in Box 26-9. The second consensus conference expanded this list to facilitate prompt clinical recognition (Box 26-11).⁸²

Signs of individual organ dysfunction are discussed later in the chapter. The two most common organs to demonstrate dysfunction in severe sepsis are the cardiovascular system and the lungs. The patient with persistent hypotension requiring vasopressor therapy despite adequate volume resuscitation is demonstrating cardiovascular dysfunction. Pulmonary dysfunction is manifested by a PaO₂/FiO₂ (fraction of oxygen in inspired air) ratio of less than 300, indicating ALI.⁸⁷ Signs indicating septic shock are hypotension despite adequate fluid resuscitation and the presence of perfusion abnormalities such as lactic acidosis, oliguria, or acute change in mentation.

The patient in severe sepsis or septic shock may present with a variety of clinical manifestations that may change dynamically as the condition progresses (Box 26-12). During the initial stage, massive vasodilation occurs in the venous and arterial beds. Dilation of the venous system leads to a decrease in venous return to the heart, which results in a decrease in the preload of the right and left ventricles. This is evidenced by a decline in the RAP and PAOP. Dilation of the arterial system results in a decrease in the afterload of the heart, as evidenced by a decrease in the SVR. The patient’s skin becomes pink, warm, and flushed as a result of the massive vasodilation. Myocardial contractility is decreased, as evidenced by a decline in the left ventricular stroke work index (LVSWI).

The heart rate rises in response to increased SNS, metabolic, and adrenal gland stimulation. If circulating volume and preload are adequate, this results in a normal-to-high CO and CI despite impaired contractility. The pulse pressure widens as the diastolic blood pressure decreases because of the vasodilation, and the systolic blood pressure increases because of the elevated CO. A full, bounding pulse develops. The net result of these changes is a relatively normal blood pressure in severe sepsis. However, as the reduction in preload and afterload becomes overwhelming and contractility fails, hypotension ensues, resulting in septic shock.

In the lungs, ventilation/perfusion mismatching develops as a result of pulmonary vasoconstriction and the formation of pulmonary microemboli. Hypoxemia occurs, and the respiratory rate increases to compensate for the lack of oxygen. Crackles develop as increased pulmonary capillary membrane permeability leads to pulmonary edema.⁷⁹

The level of consciousness starts to change as a result of decreased cerebral perfusion, immune mediator activation, hyperthermia, and lactic acidosis. This septic encephalopathy is demonstrated by acute onset of impaired cognitive functioning, or delirium, which may fluctuate during its course.⁸⁰ The patient may appear disoriented, confused, combative, or lethargic.

ABG values initially reveal hypocarbia, hypoxemia, and metabolic acidosis. This is demonstrated by a low PaO₂, low PaCO₂, and low HCO₃^– level, respectively. The respiratory alkalosis is caused by the patient’s increased respiratory rate. As pathological pulmonary changes progress and the patient becomes fatigued, the effectiveness of respirations decreases and the PaCO₂ increases, resulting in respiratory acidosis. The metabolic acidosis is the result of a lack of oxygen to the cells and the development of lactic acidemia. Serum lactate levels increase above 2 mmol/L because of anaerobic metabolism. The mixed venous oxygen saturation (SvO₂) may increase because of microcirculatory shunting or decrease because of inadequate oxygen delivery.^88,96 The white blood cell (WBC) count is elevated as part of the immune response to the invading microorganisms. The WBC differential count reveals an increase in immature neutrophils (shift to the left). This occurs because the body has to mobilize increasing numbers of WBCs to fight the infection. An elevated procalcitonin level is a valuable indicator of significant infection.^88,99 Serum glucose levels increase as part of the hypermetabolic response and the development of insulin resistance. The patient’s temperature is elevated in response to pyrogens released from the invading microorganisms, immune mediator activation, and increased metabolic activity. Urine output declines because of decreased perfusion of the kidneys. As impaired tissue perfusion develops, a variety of other clinical manifestations appear that indicate the development of MODS.

Treatment of the patient in severe sepsis or septic shock requires a multifaceted approach. The goals of treatment are to reverse the pathophysiological responses, control the infection, and promote metabolic support. This approach includes supporting the cardiovascular system and enhancing tissue perfusion, identifying and treating the infection, limiting the systemic inflammatory response, restoring metabolic balance, and initiating nutritional therapy. Dysfunction of the individual organ systems must be prevented. Early treatment reduces mortality.16,90,100,101 Guidelines for the management of severe sepsis and septic shock have been developed and updated under the auspices of the Surviving Sepsis Campaign (SSC), an international effort of more than 11 organizations to improve patient outcomes.^15,16 From these guidelines, a group (“bundle”) of selected interventions was identified as having the most impact on patient outcomes (Box 26-13). The sepsis resuscitation bundle should be implemented within the first 6 hours, and the sepsis management bundle should be implemented within the first 24 hours. More information regarding these interventions is available at the SSC website (www.survivingsepsis.org).

The patient in severe sepsis or septic shock requires immediate resuscitation of the hypoperfused state. Specific interventions are aimed at increasing cellular oxygen supply and decreasing cellular oxygen demand. These treatments include administration of fluids, vasopressors, and positive inotropic agents. Early goal-directed therapy during the first 6 hours of resuscitation improves survival¹⁰⁰ and is recommended in the SSC guidelines.^15,16 This therapy includes aggressive fluid resuscitation to augment intravascular volume and increase preload until a CVP of 8 to 12 mm Hg (12 to 15 mm Hg in mechanically ventilated patients) is achieved. Crystalloids or colloids may be used. A fluid challenge for hypovolemia should be initiated with at least 1000 mL of crystalloids or 300 to 500 mL of colloids over 30 minutes. Vasopressors (norepinephrine or dopamine as first-choice agents) should be administered as necessary to maintain a MAP of at least 65 mm Hg. These agents reverse the massive peripheral vasodilation and increase SVR. Epinephrine is recommended as an alternative agent if response to norepinephrine or dopamine is poor.¹⁶ Arterial line placement is recommended for any patient requiring vasopressor therapy. Intermittent or continuous monitoring of central venous or mixed venous oxygen saturation (SCvO₂ or SvO₂) allows evaluation of the effectiveness of oxygen delivery. If the SCvO₂ is less than 70% or the SvO₂ is less than 65% after the CVP goal is achieved, administration of packed red cells to achieve a hematocrit of at least 30%¹⁶ or inotropic stimulation with dobutamine (administered to a maximum of 20 mcg/kg/minute) to counteract myocardial depression and maintain adequate CO is recommended to obtain this goal.^16,100 The dobutamine infusion should be reduced or discontinued if a tachycardia greater than 120 beats/minute develops.¹⁰⁰

Intubation and mechanical ventilatory support are usually required to optimize oxygenation and ventilation for the patient in severe sepsis or septic shock. Ventilation with lower than traditional tidal volumes (6 versus 12 mL/kg) in patients with ALI and acute respiratory distress syndrome (ARDS) decreases mortality.¹⁰² SSC guidelines recommend the goals of 6 mL/kg of predicted body weight and plateau pressures no more than 30 cm H₂O for patients with severe sepsis or septic shock with ALI or ARDS.¹⁶ Increased PaCO₂ may result from this therapy and is acceptable if tolerated as evidenced by hemodynamic stability. Ventilator settings should include positive end-expiratory pressure and be adjusted to provide the patient with a PaO₂ greater than 70 mm Hg. Patients receiving mechanical ventilation should be maintained in a semirecumbent position with the head of the bed raised to 45 degrees to decrease the incidence of ventilator-associated pneumonia.¹⁶ Prone positioning should be considered in the septic patient with ARDS requiring high levels of oxygen.¹⁶ Sedation protocols using intermittent bolus or continuous infusion using a standardized sedation scale and specific goals are recommended for all patients requiring mechanical ventilation. Daily interruption of sedative infusions to allow wakefulness and reevaluation of sedation needs reduces duration of mechanical ventilation and is recommended.¹⁶ Neuromuscular blocking agents should be avoided, if possible, to prevent prolonged blockade after discontinuation.¹⁶

A key measure in the treatment of septic shock is finding and eradicating the cause of the infection. At least two blood cultures plus urine, sputum, and wound cultures should be obtained to find the location of the infection before antibiotic therapy is initiated.¹⁶ Antibiotic therapy should be started within 1 hour of recognition of severe sepsis without delay for cultures.¹⁶ Each hour of delay is associated with a substantial drop in the survival rate.¹⁰¹ If the microorganism is unknown, antiinfective therapy with one or more agents known to be effective against likely pathogens should be initiated, with daily reassessment of the regimen. Combination therapy is recommended for known or suspected Pseudomonas infection and for neutropenic patients but should be limited to less than 3 to 5 days.¹⁶ A specific source of infection should be established within 6 hours of presentation.¹⁶ Surgical intervention to débride infected or necrotic tissue or to drain abscesses may be necessary to facilitate removal of the septic source.¹⁶ Intravascular devices that may be the source of the infection should be removed after establishment of alternative vascular access.

Intravenous corticosteroids reduce mortality in catecholamine-dependent septic shock patients with relative adrenal insufficiency.¹⁰⁷ Intravenous hydrocortisone is recommended only for the patient in septic shock who is poorly responsive to fluid resuscitation and vasopressor therapy.¹⁶ Doses greater than 300 mg/day may be harmful and should not be used and steroid therapy should be weaned when vasopressors are no longer required.¹⁶

Continuous infusion of insulin and glucose to maintain a blood glucose level of 150 mg/dL or less improves outcomes⁴² and is recommended by SSC guidelines after initial stabilization.¹⁶ Glucose levels should be monitored every 1 to 2 hours until stable and then every 4 hours. Low glucose levels measured by capillary testing may be inaccurate in this population.¹⁶ Platelets should be administered when counts are less than 5000/mm³ and red blood cell transfusions are recommended when the hemoglobin level is less than 7.0 g/dL to obtain a target value of 7 to 9 g/dL.¹⁶ Stress ulcer prophylaxis using histamine₂ (H₂) blockers or proton-pump inhibitors and DVT prophylaxis are recommended for all patients with severe sepsis or septic shock. The SCCM guidelines recommend against the use of sodium bicarbonate for lactic acidemia if the pH is equal to or greater than 7.15.¹⁶ Low-dose dopamine infusion for renal protection is not beneficial and should not be used.¹⁶

The initiation of nutritional therapy is critical in the management of the patient in severe sepsis or septic shock. The goal is to improve the patient’s overall nutritional status, enhance immune function, and promote wound healing. A daily caloric intake of 25 to 30 kcal/kg of usual body weight is recommended. The enteral route is preferred. The ideal nutritional supplement for the patient in septic shock should be high in protein because of the metabolic derangements that develop in the hypermetabolic state. The amount of protein calories given depends on the patient’s nitrogen balance. In early sepsis, the mix of nonprotein calories may be divided evenly between carbohydrates and fats. In the later stages, significant alterations in fat metabolism occur, and the lipid content should be limited to 10% to 15% of the total nonprotein calories. Specific nutritional therapies to reduce the inflammatory and hypermetabolic responses associated with sepsis, such as antioxidant supplementation and feeding with long-chain n-3 polyunsaturated fatty acids, are the source of much debate and are being evaluated.^8,108–111 Glutamine is considered by some to be an essential amino acid in critically ill patients and has the most empirical support.^{88,108,109,111} Arginine has produced negative outcomes and is not recommended.¹¹⁰

Prevention of severe sepsis and septic shock is one of the primary responsibilities of the nurse in the critical care area. These measures include the identification of patients at risk and reduction of their exposure to invading microorganisms. Hand washing, aseptic technique, and an understanding of how microorganisms can invade the body are essential components of preventive nursing care. Early identification allows for early treatment and decreases mortality.80 Box 26-14 depicts a simple screening tool for identifying patients with severe sepsis.

The patient in septic shock may have any number of nursing diagnoses, depending on the progression of the process (Nursing Diagnosis Priorities Box on Septic Shock). Nursing priorities are directed toward (1) early identification of sepsis syndrome, (2) administering prescribed fluids and medications, (3) providing comfort and emotional support, and (4) maintaining surveillance for complications. Continual observation to detect subtle changes that indicate the progression of the septic process is also very important.

Evidence-based guidelines for the management of the patient with severe sepsis or septic shock are listed in the Evidence-Based Practice box on Severe Sepsis and Septic Shock Management Guidelines.

Organ dysfunction may be a direct consequence of the insult (primary MODS) or can manifest latently and involve organs not directly affected in the initial insult (secondary MODS). Patients can experience both primary and secondary MODS (Figure 26-6).

Primary MODS “directly results from a well-defined insult in which organ dysfunction occurs early and is directly attributed to the insult itself”³ and accounts for only a small fraction of MODS cases. Direct insults initially cause localized inflammatory responses. Examples of primary MODS include the immediate consequences of posttraumatic pulmonary failure, thermal injuries, acute tubular necrosis, or invasive infections.¹¹⁵ These cellular or microcirculatory events may lead to a loss of critical organ function induced by failure of delivery of oxygen and substrates, coupled with the inability to remove end-products of metabolism.^112,115,116 The inflammatory response in primary MODS has a less apparent presentation and may resolve without long-term implications. This primary dysfunction is thought to set the system up for a more observable inflammatory response leading to secondary MODS.¹¹²

Secondary MODS is a consequence of widespread systemic inflammation that results in dysfunction of organs not involved in the initial insult.^81,82 Secondary MODS develops latently after an initial insult. The early impairment of organs normally involved in immunoregulatory function, such as the liver and the GI tract, intensifies the host response to the insult. It is postulated that the initial insult “primes” the inflammatory system in such a way that a mild second insult may perpetuate a hyperinflammatory response.¹¹⁷

Systemic inflammatory response syndrome (SIRS) or sepsis is a common initiating event in the development of secondary MODS. The systemic inflammatory response is an abnormal host response characterized by generalized inflammation in organs remote from the initial insult. SIRS is widespread inflammation or clinical responses to inflammation that occurs in patients suffering a variety of insults. Clinical conditions and manifestations associated with SIRS are listed in Box 26-15. These insults produce similar or identical systemic inflammatory responses, even in the absence of infection. SIRS is diagnosed when at least two of four clinical manifestations occur in the high-risk patient. Manifestations of SIRS must represent an acute alteration from the patient’s normal baseline and must not be related to other causes (e.g., neutropenia from chemotherapy). Organ dysfunction or failure, such as acute lung injury (ALI), acute renal failure, and MODS, is a complication of SIRS.^{81,82,112,115} In epidemiological studies, SIRS was found to occur in one third of all hospitalized patients, in 50% to 93% of all patients in critical care units, and in about 80% of all patients in surgical critical care units.^118,119

When SIRS is a result of infection, the term sepsis is used. Severe sepsis is sepsis with hypoperfusion or systemic manifestations of hypoperfusion. Septic shock is sepsis-induced hypotension despite fluid resuscitation. SIRS, sepsis, severe sepsis, and septic shock represent a hierarchical continuum of the inflammatory response to infection.¹⁶ Although infection and shock remain the most common precipitating factors, any disease that can induce a major inflammatory response is capable of initiating the events that lead to MODS.¹¹⁵

When SIRS is not contained locally, several consequences occur that lead to organ dysfunction, including intense, uncontrolled activation of inflammatory cells; direct damage of vascular endothelium; disruption of immune cell function; persistent hypermetabolism; and maldistribution of circulatory volume to organ systems.^112,115 Inflammation becomes a systemic, self-perpetuating process that is inadequately controlled and results in organ dysfunction.^115,120 During hypermetabolism, changes occur in cellular anabolic and catabolic function, resulting in autocatabolism. Autocatabolism manifests as a severe decrease in lean body mass, severe weight loss, anergy, and increased cardiac output and VO₂ resulting from profound alterations in carbohydrate, protein, and fat metabolism.^112,121 Concurrently, GI, hepatic, and immunological dysfunction may occur, which intensifies the SIRS.¹²² Clinical consequences may affect gut function, wound healing, muscles wasting, host response, respiratory function, and continued promotion of the hypermetabolic response.¹²¹

Not all patients develop MODS from SIRS. The development of MODS appears to be associated with failure to control the source of inflammation or infection, persistent hypoperfusion, flow-dependent oxygen consumption (VO₂), or the continued presence of necrotic tissue.^113,115

Secondary MODS results from altered regulation of the patient’s acute immune and inflammatory responses. Dysregulation, or failure to control the host inflammatory response, leads to the excessive production of inflammatory cells and biochemical mediators that cause widespread damage to vascular endothelium and organ damage.112,115,120 The critically ill patient’s compromised immune state also fosters an environment conducive to organ failure.

The definitive clinical course of secondary MODS has not been completely identified. One theory suggests that organ dysfunction may occur in a sequential or progressive pattern. This pattern begins with the lungs, the most commonly affected major organ, and then goes on to involve the liver, gut, and kidneys. A late component is cardiac and, sometimes, bone marrow dysfunction. Neurological and autonomic system impairment may occur and propagate the progression of organ failure and is associated with illness severity and mortality.¹²³ Organs may fail simultaneously; for example, renal dysfunction may take place concurrently with hepatic dysfunction. After the initial insult and resuscitation, patients develop persistent hypermetabolism, a metabolic consequence of sustained systemic inflammation and physiological stress, followed closely by pulmonary dysfunction, manifested as ALI.

Certain cellular and biochemical activity evoke the inflammatory and immune responses implicated in SIRS and MODS. The mediators associated with SIRS and MODS can be classified as inflammatory cells, biochemical mediators, or plasma protein systems (Box 26-16). Activation of one mediator often leads to activation of another. The biological activity of inflammatory cells, biochemical mediators, and plasma protein systems and how they work in concert to cause SIRS and MODS have not been totally determined.¹²⁴

Secondary MODS is a systemic disease with organ-specific manifestations. Organ dysfunction is influenced by numerous factors, including organ host defense function, response time to the injury, metabolic requirements, organ vasculature response to vasoactive drugs, organ sensitivity to damage, and physiological reserve. The responses of the gastrointestinal, hepatobiliary, cardiovascular, pulmonary, renal, and hematological systems are discussed in the following paragraphs. Clinical manifestations of organ dysfunction are outlined in Box 26-17.

The patient with MODS requires multidisciplinary collaboration in clinical management, including fluid resuscitation and hemodynamic support (when appropriate), prevention and treatment of infection, maintenance of tissue oxygenation, nutritional and metabolic support, comfort and emotional support, and support for individual organ function.81,124 The use of investigational therapies may be part of the patient’s clinical management. Collaborative management of the patient with MODS is outlined in the Collaborative Management Box on Multiple Organ Dysfunction Syndrome.

Patients are assessed closely for inflammation and infection. Subtle expressions of infection warrant investigation. Nursing measures include strict adherence to standards of practice to prevent infection. Practices related to infection control with invasive hemodynamic monitoring, urinary catheters, endotracheal tubes, intracranial pressure monitoring devices, total parenteral nutrition (TPN), and wound care must be stringent to prevent further infection. Prevention of a concomitant ventilator-associated pneumonia or aspiration pneumonia is a priority.^16,141

Measures to limit tissue oxygen consumption include (1) administering analgesics and sedatives, (2) positioning the patient for comfort, (3) limiting activities, (4) offering support to reduce anxiety, (5) providing a calm and quiet environment, and (6) teaching the patient about the condition. Measures to enhance tissue oxygen supply include administering supplemental oxygen, monitoring the patient’s respiratory status, and administering prescribed fluids and medications.